Abstract
Abstract: :
Purpose: Increasing evidence indicates that estrogen plays a protective role against cataract formation. This study was designed to understand the molecular mechanisms underlying estrogen's action. Method: Lenses from normal rats aged 3 weeks, 17 weeks (normal and ovariectomized) and 9 months were cultured in four conditions: control, 0.15 ng/ml TGF-ß2, 10-8 M estradiol, or TGF-ß2 plus estradiol. Individual lenses (4-8 lenses/condition/time point) were harvested at days 2, 3, and 7 for morphology and RT-PCR. Results: Gene expression of α-smooth muscle actin, a molecular marker for subcapsular and secondary cataracts, increased 10 to 15-fold after 2 days of incubation in TGF-ß2. This up-regulation preceded the formation of cataracts by 4-5 days. The induction occurred in all of the 9-month old animals and in three-fourths of the 3-week-old and 17-week-old animals. Estradiol blocked the induction of α-smooth muscle actin in 9 month-old female rats, but not in 9-month-old male rats. In 17-week-old animals, the estradiol effect was, again, more frequent in female lenses than male lenses, while, in 3-week-old animals, the effect was equal (50% of lenses) in both sexes. Conclusion: Previously, Hales et al. showed that estradiol prevents cataract formation in lenses of ovariectomized females. We have expanded this finding by showing that estradiol affects the genetic program of the lens by suppressing the induction of α-smooth muscle actin gene expression. Age- and gender-related differences were observed.
Keywords: 338 cataract • 417 gene/expression